The overall objective of this project is to develop a medical fibrin sealant from fish plasma. Commercial aquaculture rears millions of large salmonids, and the plasma from these fish offers an unexplored and innovative source of highly conserved clotting factors. A major advantage is safety from mammalian infectious agents due to the remote phylogeny of fishes and differences in body temperature. Specific aims are to maximize fibrinogen and thrombin content of fish plasma, develop practical methods for harvest and extraction of these substances, characterize fish plasma clotting factors and a fish fibrin sealant in vitro, and conduct initial tests of this sealant in rats. Plasma fibrinogen and thrombin will be tested and compared in trout (Oncorhynchus mykiss) and salmon (Salmo salar) at different reproductive stages and under different environmental conditions, and optimum harvest conditions determined. Clot and sealant characteristics will be determined in vitro by rheologic testing and by incubation in human plasmin, and in vivo by comparing strength of rat skin incisions treated with fish fibrin sealant and a commercial sealant. PROPOSED COMMERCIAL APPLICATION: A fibrin sealant derived from fish plasma would offer safety from mammalian infectious agents, and possibly more rapid clotting, and greater clot stability. As a commercial product, it could capture a large portion of the $500 million U. S. market for fibrin sealants.